Denali Therapeutics Announces New Data and Expansion of Its Blood-Brain Barrier (BBB)-Crossing Enzyme Replacement Therapy Programs at WORLDSymposium

• New data show additional improvement and stabilization in clinical outcomes in MPS II with 104 weeks of tividenofusp alfa (DNL310) treatment in the open-label, single-arm Phase 1/2 study; sustained normalization of CSF heparan sulfate and robust, sustained reduction in neurofilament light chain (NfL) observed
  
• Announcing initiation of dosing with DNL126 (ETV:SGSH) in Phase 1/2 study in MPS IIIA and new supportive data with MPS IIIA mice showing reductions in heparan sulfate correlated with improvements in cognitive function

SOUTH SAN FRANCISCO, Calif., Feb. 07, 2024 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (NASDAQ: DNLI), a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases and lysosomal storage diseases, today announced new data presentations highlighting the broad potential of its BBB-crossing enzyme replacement therapies in development for the treatment of mucopolysaccharidoses (MPS). New clinical data on tividenofusp alfa (DNL310) in MPS II (Hunter syndrome) and mouse model data on DNL126 (ETV:SGSH) in MPS IIIA (Sanfilippo syndrome type A) are being presented this week at the 20^th Annual WORLDSymposium in San Diego, California.

“It is exciting to see new clinical outcomes data, now up to two years of treatment with tividenofusp alfa,” said Joseph Muenzer, M.D., Ph.D., Bryson Distinguished Professor in Pediatric Genetics, University of North Carolina at Chapel Hill, who presented the Phase 1/2 data on tividenofusp alfa in MPS II. “The robust and sustained biomarker reductions, including NfL, and the effects on measures of behavior, cognition, hearing, liver volumes and growth indicate positive treatment effects in brain and somatic tissues. Denali’s BBB-crossing enzyme replacement approach has the potential to prevent cognitive and behavioral manifestations in MPS IIIA. Together with Denali and the MPS community, I am passionately advocating for the fastest path to approval to enable new treatment options for people living with MPS diseases.”

In addition, new data on somatic outcomes from the same study of tividenofusp alfa will be presented for the first time by Barbara Burton, M.D., Professor of Pediatrics, Genetics, Genomics and Metabolism at Feinberg School of Medicine in Chicago. The Phase 1/2 results demonstrate normalization of enlarged liver and spleen volumes and maintenance of normal growth compared to healthy boys in almost all participants. New two-year peripheral biomarker data demonstrate high magnitude and sustained reduction of urine heparan sulfate and dermatan sulfate, including in participants who switched from standard-of-care enzyme replacement therapy to tividenofusp alfa, suggesting enhanced peripheral activity. Tividenofusp alfa treatment continued to be generally well tolerated.